Abstract
Previous studies have shown that some dysregulated miRNAs are involved in radioresistance of tumor cells. Here, we identified significantly decreased miR-424 expression in radioresistant cervical cancer cells and specimens from cervical cancer patients with radioresistance compared to their radiosensitive parental cells and specimens from radiosensitive patients, respectively. Ectopic expression of miR-424 significantly increased radiation-induced DNA damage, cell apoptosis and G2/M cell cycle arrest in radioresistant cervical cancer cells. Notably, miR-424 agomiR treatment can sensitize radioresistant cervical cancer cells to radiation in a xenograft model. Furthermore, we demonstrated that miR-424 regulated radiosensitivity by directly targeting aprataxin. Taken together, these findings suggest that miR-424 acts as a radiosensitizing miRNA and reveal a new therapeutic strategy for radioresistant cervical cancers.
Highlights
Cervical cancer remains one of the leading gynecological malignancies affecting women worldwide [1], and radiotherapy is the most common intervention, as either a primary or adjuvant therapy [2, 3]
We observed, for the first time, that the miR-424 expression was remarkably decreased in specimens from cervical cancer patients with radioresistance compared to specimens from radiosensitive patients
Our investigation further demonstrated that ectopic expression of miR-424 can significantly enhance the radiosensitivity of radioresistant cervical cancer cells in vitro and in vivo, which suggests that the ectopic expression of miR-424 may be a novel strategy for enhancing radiosensitivity in cervical cancer patients
Summary
Cervical cancer remains one of the leading gynecological malignancies affecting women worldwide [1], and radiotherapy is the most common intervention, as either a primary or adjuvant therapy [2, 3]. The mechanism of cellular radiosensitivity regulation remains unclear in cervical cancer. Recent studies show that radiotherapy can dysregulate some miRNAs, which significantly contributes to the development of radioresistance in cervical cancer [6, 7] by activating DNA repair pathways [8, 9]. Because a single miRNA can target hundreds of genes, affecting a large cellular signaling network, single miRNAs play key roles in cancer progression [12]. Investigating the role of each dysregulated miRNA and its corresponding mechanism is very important in cancer [13]. Our understanding of the potential roles of miRNAs in the radiation treatment response for cervical cancer remains limited
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